Recent Advances of Azobenzene-Based Photoresponsive Molecular Switches for Protein-Targeted Photopharmacology

Azobenzene derivatives constitute a prototypical class of photoresponsive molecular switches with broad utility in synthetic chemistry and biomedical research, owing to their distinctive physicochemical properties. Recent molecular engineering has enabled red-shifted photoisomerization into the visible biological window, thereby enhancing tissue penetration and reducing phototoxicity. This review systematically surveys contemporary advances in azobenzene-based photoswitchable systems with a specific focus on medicinal chemistry and photopharmacology. Emphasis is placed on rational design strategies-including ortho-functionalization, heteroaryl substitution, and bridged diazocine scaffolds-that improve photophysical properties, thermal stability, and photostationary state distributions. Particular attention is devoted to the integration of these novel azobenzene motifs as privileged pharmacophores, highlighting their emerging therapeutic applications in neurological modulation, enzyme inhibition, receptor targeting, and oncology, as well as their translational potential in drug discovery and photodynamic therapy.